Experimental Brain Research

Alcohol intoxication is the cause of many falls requiring emergency care. The control of upright standing balance is complex and comprises contributions from several partly independent mechanisms like coordination, feedback and feedforward control and adaptation. Analysis of the segmental body movement coordination offers one option to detect the severity of balance problems. The study aims were (1) to investigate whether alcohol intoxication at 0.06 and 0.10% blood alcohol concentration (BAC) affected the segmental movement pattern under unperturbed and perturbed standing; (2) whether alcohol affected the ability for movement pattern adaptation; (3) whether one's own subjective feeling of drunkenness correlated to the movement pattern used. Twenty-five participants (13 women and 12 men, mean age 25.1 years) performed tests involving alcohol intoxication. Body movements were recorded at five locations (ankle, knee, hip, shoulder and head) during quiet standing and pseudorandom pulses of calf muscle vibration for 200 s with eyes closed or open. There was no significant effect of alcohol on the general movement pattern in unperturbed stance or on adaptation. However, when balance was repeatedly perturbed, knee movements became significantly less correlated to other body movements over time at 0.10% BAC and when visual information was unavailable, suggesting that the normal movement pattern could not be maintained for a longer period of time while under 0.10% BAC intoxication. Subjective feelings of drunkenness correlated often with a changed upper body movement pattern but less so with changed knee movements. Thus, an inability to relate drunkenness with changed knee movements may be a contributing factor to falls in addition to the direct effect of alcohol intoxication.

This study examined long-term (up to 27 days) effects of maintained vision reversal on (i) smooth visual tracking with head still, (ii) oculomotor response to actively, generated head oscillation and (iii) "spontaneous" saccades. Dove prism goggles produced horizontal, but not vertical (sagittal plane), vision reversal. Eye movements were recorded by EOG; head movements by an electro-magnetic search coil. Both visual tracking and saccade dynamics remained unchanged throughout. In contrast, both the ocular response to active head oscillations (goggles off and subject looking at a stationary target) and associated retinal image blur showed substantial and retained adaptive changes, akin to those previously found in the vestibulo-ocular reflex as tested in darkness at 0.17 Hz. However, several addition unexpected results emerged. First, in the fully adapted state smooth eye movements tended to be of reversed phase in the range 0.5-1.0 Hz (in spite of normal vision during tests), but of normal phase from about 2 Hz and above (in spite of negligible visual tracking in this upper range). Second, after permanent removal of the inverting goggles, this peculiar frequency response of the fully adapted state quickly (36 h) reverted to a dynamically simpler condition manifest as retained (2-3 weeks) attenuation of gain (eye vel./head vel.) which, as in control conditions, was monotonically related to frequency. From these two findings it is inferred that the fully adapted state may have comprised two separate components: (i) A "simple element of monotonic and long-lasting gain attenuation and (ii) a "complex", frequency labile, element which could be quickly rejected. Dynamic characteristics of the putative "complex" element were estimated by vectorial subtraction of the "simple" one from that of the fully adapted condition. The outcome suggests that the inferred "complex" condition might represent a predictive element. Two further findings are reported: (i) Substantially different vectors of the adapted response were obtained with normal and reversed vision at 3.0 Hz head oscillation, indicating a novel visual tracking. (ii) During head oscillation in the vesicle sagittal plane (in which vision was not reversed) there was never any image blur, indicating high geometric specificity in the adaptive process.

The amygdaloid complex and hippocampal region contribute to emotional activities, learning, and memory. Mounting evidence suggests a primary role for serotonin (5-HT) in the physiological basis of memory and its pathogenesis by modulating directly the activity of these two areas and their cross-talk. Indeed, both the amygdala and the hippocampus receive remarkably dense serotoninergic inputs from the dorsal and median raphe nuclei. Anatomical, behavioral and electrophysiological evidence indicates the 5-HT2A receptor as one of the principal postsynaptic targets mediating 5-HT effects. In fact, the 5-HT2A receptor is the most abundant 5-HT receptor expressed in these brain structures and is expressed on both amygdalar and hippocampal pyramidal glutamatergic neurons as well as on γ-aminobutyric acid (GABA)-containing interneurons. 5-HT2A receptors on GABAergic interneurons stimulate GABA release, and thereby have an important role in regulating network activity and neural oscillations in the amygdala and hippocampal region. This review will focus on the distribution and physiological functions of the 5-HT2A receptor in the amygdala and hippocampal region. Taken together the results discussed here suggest that 5-HT2A receptor may be a potential therapeutic target for those disorders related to hippocampal and amygdala dysfunction.

Lesions of nigrostriatal dopaminergic neurons as seen in Parkinson's disease (PD) increase orofacial responses to serotonergic (5-HT) agonists in rodents. Although this response to 5-HT agonists has been related to aberrant signalling in the basal ganglia, a group a subcortical structures involved in the control of motor behaviours, it deserves additional studies with respect to the specific loci involved. Using measurements of orofacial activity, as well as single-cell recordings in vivo, we have studied the role of the entopeduncular nucleus (EPN; equivalent to the internal globus pallidus of primates), an output structure of basal ganglia, in the hypersensitized responses to a 5-HT agonist in sham- or unilaterally dopamine-depleted rats. Intra-EPN injections of Ro 60-0175 (0.3 and 1 μg/100 nl) promoted robust oral movements in 6-OHDA rats without affecting oral activity in sham-depleted rats. Peripheral administration of Ro 60-0175 (3 mg/kg ip) decreased EPN neuronal firing rate in 6-OHDA rats compared to sham-depleted rats. Such an effect was also observed when the agonist (0.2 μg/20 nl) was locally applied onto EPN neurons. These data demonstrate the contribution of EPN to hypersensitized responses to 5-HT agonists in a rat model of PD.

Individuals with schizotypal personality disorder or high scores in questionnaires measuring schizotypy are at high risk for the development of schizophrenia and they also share some of the same phenotypic characteristics such as eye-tracking dysfunction (ETD). The question arises whether these individuals form a distinct high-risk group in the general population or whether schizotypy and ETD co-vary in the general population with no distinct cutoff point for a high-risk group. A large sample of military conscripts aged 18-25 were screened using oculomotor, cognitive and psychometric tools for the purposes of a prospective study on predisposing factors for the development of psychosis. Schizotypy measured using the perceptual aberration scale (PAS) and the schizotypal personality questionnaire (SPQ), anxiety and depression, measured using the Symptom Checklist 90-R, had no effect on pursuit performance in the total sample. Small groups of individuals with very high scores in schizotypy questionnaires were then identified. These groups were not mutually exclusive. The high PAS group had higher root-mean-square error scores (a quantitative measure for pursuit quality) than the total sample, and the high disorganized factor of SPQ group had lower gain and higher saccade frequencies in pursuit than the total sample. The presence of significant differences in pursuit performance only for predefined high schizotypy groups favors the hypothesis that individuals with high schizotypy might present one or more high-risk groups, distinct from the general population, that are prone to ETD as that observed in schizophrenia.

Prevention of testosterone aromatization in the female rat pups by perinatal treatment with 1,4,6 androstatriene-3,17-dione (ATD) induces an important defeminization as shown by a reduction of fluctuations of LH release after castration and estradiol implantation. The fact that, under our in vitro experimental conditions, ATD is able to displace testosterone binding in the hypothalamus whereas estradiol does not, confirms the hypothesis that ATD acts on aromatase. The most attractive explanation for the defeminization effect of ATD is then an estrogen-like action of ATD.

Delayed cell death following ischemic brain injury has been linked to alterations in gene expression. In this study we have evaluated the upregulation of several genes associated with delayed cell death (c-fos, bax, and bcl-2) during the initial 24 h of transient middle cerebral artery occlusion (MCAo) in the rat and the effects of postinjury treatment with the NR2B subunit specific NMDA receptor antagonist CGX-1007 (Conantokin-G, Con-G). C-fos mRNA levels peaked at 1 h postinjury in both cortical and subcortical ischemic brain regions (30-fold increase), remained elevated at 4 h and returned to within normal, preinjury levels 24 h postinjury. The increase in mRNA levels correlated to increased protein expression in the entire ipsilateral hemisphere at 1 h. Regions of necrosis at 4 h were void of C-Fos immunoreactivity with continued upregulation in surrounding regions. At 24 h, loss of C-Fos staining was observed in the injured hemisphere except for sustained increases along the border of the infarct and in the cingulate cortex of vehicle treated rats. CGX-1007 treatment reduced c-fos expression throughout the infarct region by up to 50%. No significant differences were measured in either bcl-2 or bax mRNA expression between treatment groups. However, at 24 h postinjury CGX-1007 treatment was associated with an increase in Bcl-2 immunoreactivity that correlated to a reduction in DNA fragmentation. In conclusion, CGX-1007 effectively attenuated gene expression associated with delayed cell death as related to a neuroprotective relief of cerebral ischemia.

There is evidence that men experience more sexual arousal than women but also that women in mid-luteal phase experience more sexual arousal than women outside this phase. Recently, a few functional brain imaging studies have tackled the issue of gender differences as pertaining to reactions to erotica. The question of whether or not gender differences in reactions to erotica are maintained with women in different phases has not yet been answered from a functional brain imaging perspective. In order to examine this issue, functional MRI was performed in 22 male and 22 female volunteers. Subjects viewed erotic film excerpts alternating with emotionally neutral excerpts in a standard block-design paradigm. Arousal to erotic stimuli was evaluated using standard rating scales after scanning. Two-sample t-test with uncorrected P < 0.001 values for a priori determined region of interests involved in processing of erotic stimuli and with corrected P < 0.05 revealed gender differences: Comparing women in mid-luteal phase and during their menses, superior activation was revealed for women in mid-luteal phase in the anterior cingulate, left insula, and orbitofrontal cortex. A superior activation for men was found in the left thalamus, the bilateral amygdala, the anterior cingulate, the bilateral orbitofrontal, bilateral parahippocampal, and insular regions, which were maintained at a corrected P in the amygdala, the insula, and thalamus. There were no areas of significant superior activation for women neither in mid-luteal phase nor during their menses. Our results indicate that there are differences between women in the two cycle times in cerebral activity during viewing of erotic stimuli. Furthermore, gender differences with women in mid-luteal phases are similar to those in females outside the mid-luteal phase.

1.The glomerulus in the cerebellar granular layer is composed of the three elements; the mossy fibre terminal, the granule cell dendrites and the Golgi cell axons. The afferent input to the cerebellar cortex through the glomerulus, the mossy fibre-granule cell relay (M.G.R.), and its inhibitory control by the Golgi cells were studied by recording, a) extracellular field potentials in the granular and molecular layers, b) unitary spikes of granule cells, and c) intracellular postsynaptic potentials in Purkinje cells.2.Mossy fibres were activated by juxta-fastigial, transfolial, lateral cuneate nucleus and radial nerve stimulation. Stimulation of an adjacent folium (transfolial stimulation) could excite branches of mossy fibres under the stimulating electrode which supply other branches also to the folium under the recording electrode. This technique was utilized to distinguish the response due to mossy fibre activation from those due to the climbing fibre and Purkinje cell axons.3.These stimulations resulted in, through the M.G.R., a powerful activation of granule cells whose axons (parallel fibres) excited in turn the Purkinje cells and the inhibitory interneurones, including the Golgi cells, in the molecular layer.4.Field potentials and unitary spikes due to granule cell activity elicited by the stimulation of mossy fibres were markedly depressed for hundreds of milliseconds after the direct stimulation of parallel fibres (LOC stimulation). The postsynaptic potential in Purkinje cells evoked by mossy fibre activation was also depressed by the conditioning LOC stimulation in the same manner. The “spontaneous” background activities recorded from granule cells as unitary spikes and from Purkinje cells as inhibitory synaptic noise were silenced for hundreds of milliseconds after the LOC stimulation.5.These depressions indicate that the parallel fibre activation evokes an inhibitory action upon M.G.R. On anatomical grounds this inhibition can be mediated only by the Golgi cell, and it is postulated that the inhibitory action is postsynaptic upon the dendrites of granule cells.6.It is concluded that the Golgi cell inhibition regulates the mossy fibre input to the cerebellar cortex at the M.G.R. by a form of negative feed-back.

Literature on the therapeutic efficacy of free radical scavengers suggests that drugs that are able to cross the blood-brain barrier are more effective in protecting the brain from ischemic damage. However, the exact mechanisms by which brain-penetrating antioxidants act have yet not been delineated. We compared the neuroprotective potential of the newly discovered pyrrolopyrimidine U-101033E with that of alpha-phenyl-N-tert-butyl nitrone (PBN) and investigated their influence on cerebral blood flow. Thirty male Sprague-Dawley rats were subjected to 90 min of middle cerebral artery (MCA) occlusion by an intraluminal filament. Local cerebral blood flow (LCBF) was bilaterally recorded by laser Doppler flowmetry. Neurological deficits were quantified daily. Infarct volume was assessed after 7 days. MCA occlusion reduced ipsilateral LCBF to 20-30% of baseline. After reperfusion, postischemic hyperemia was followed by a decrease in LCBF to about 70% of baseline. There was no difference in LCBF among groups. U-101033E improved neurological function and reduced infarct volume by 52% (P < 0.05). Improvement of neurological function and reduction of infarct volume (-25%) in animals treated with PBN was not significant. We conclude that U-101033E has superior neuroprotective properties compared with PBN. Neither drug improves blood flow during ischemia and 1 h of reperfusion. The mechanisms by which these brain-penetrating antioxidants act remain to be clarified.

Monkeys demonstrate improved contrast sensitivity at the goal of a planned memory-guided saccade (Science 299:81-86, 2003). Such perceptual improvements have been ascribed to an endogenous attentional advantage induced by the saccade plan. Speeded reaction times have also been used as evidence for attention. We therefore asked whether the attentional advantage at the goal of a planned memory-guided saccade led to speeded manual reaction times following probes presented at the saccade goal in a simple detection task. We found that monkeys showed slower manual reaction times when the probe appeared at the memorized goal of the planned saccade when compared to manual reaction times following a probe that appeared opposite the saccade goal. Flashing a distractor at the saccade goal after target presentation appeared to slow reaction times further. Our data, combined with prior results, suggest that a spatially localized inhibition operates on the neural representation of the saccade goal. This inhibition may be closely related or identical to the processes underlying inhibition-of-return. We also found that if the same detection task was interleaved with a difficult perceptual discrimination task, manual reaction times became faster when the probe was at the saccade goal. We interpret these results as being an effect of task difficulty; the more difficult interleaved task may have engaged endogenous attentional resources more effectively, allowing it to override the inhibition at the saccade goal. We construct and discuss a simple working hypothesis for the relationship between the effects of prior attention on neural activity in salience maps and on performance in detection and discrimination tasks.

Previous studies suggest that a population of precursor cells from the developing and adult mouse striatum can be expanded in culture using serum-free, N2-supplemented medium and mitogenic factors such as epidermal growth factor (EGF). Here we show that EGF-responsive precursor cells from embryonic rat striatum and mesencephalon can also be expanded in culture, incorporate bromodeoxy uridine (BrDU) and develop into spheres that either adhere to the surface of the culture dish or float freely in the medium. Addition of B27, a medium supplement that increases neuronal survival in primary CNS cultures, resulted in a tenfold increase in the number of proliferating cells in vitro over the first week. The effects of B27-supplemented medium on precursor cell survival were only seen when primary cultures were used, such that dividing cells grown in B27 for 1 week could then be transferred to either B27 or N2 medium and show similar survival and division rates in response to EGF. After 1, 2 or 4 weeks of growth in B27-supplemented medium, dissociated precursor cells from either striatal or mesencephalic cultures could be differentiated when exposed to a poly-l-lysine-coated substrate in serum and EGF-free medium supplemented with B27. These cells then matured into a mixed culture containing neurons (approximately 35% of cells), astrocytes (approximately 44% of cells), and oligodendrocytes (approximately 10% of cells), based on immunocytochemical staining with microtuble-associated protein (MAP2), glial fibriallary acidic protein and galactocerebrosidase. When whole spheres of precursor cells were allowed to differentiate, every one examined was found to generate neurons, astrocytes and oligodendrocytes in similar proportions.(ABSTRACT TRUNCATED AT 250 WORDS)

This paper provides evidence that the ventral prefrontal cortex plays a role in the learning of tasks in which subjects must learn to associate visual cues and responses. Imaging with both positron-emission tomography (PET) and functional magnetic-resonance imaging (fMRI) reveals learning-related increases in activity when normal subjects learn visual associative tasks. Evidence is also presented from an event-related fMRI study that activity in this area is time-locked both to the presentation of the visual stimuli and also to the time of the motor response. Finally, it is shown in a study of monkeys that removal of the ventral prefrontal area 12 (including 45 A) impairs the ability of monkeys to relearn a visual associative task (visual matching), even though there were no demands on working memory. It is, therefore, proposed that the ventral prefrontal cortex constitutes part of the circuitry via which associations are formed between visual cues and the actions or choices that they specify. On the basis of the existing anatomical and electrophysiological data, it is argued that the prefrontal cortex is the only area that can represent cues, responses and outcomes.

Perturbations of the synaptic handling of glutamate have been implicated in the pathogenesis of brain damage after transient ischemia. Notably, the ischemic episode is associated with an increased extracellular level of glutamate and an impaired metabolism of this amino acid in glial cells. Glutamate uptake is reduced during ischemia due to breakdown of the electrochemical ion gradients across neuronal and glial membranes. We have investigated, in the rat hippocampus, whether an ischemic event additionally causes a reduced expression of the glial glutamate transporter GLT1 (Pines et al. 1992) in the postischemic phase. Quantitative immunoblotting, using antibodies recognizing GLT1, revealed a 20% decrease in the hippocampal contents of the transporter protein, 6 h after an ischemic period lasting 20 min induced by four vessel occlusion. In situ hybridization histochemistry with 35S labelled oligonucleotide probes or digoxigenin labelled riboprobes directed to GLT1 mRNA showed a decreased signal in the hippocampus, particularly in CA1. This reduction was more pronounced at 3 h than at 24 h after the ischemic event. We conclude that the levels of GLT1 mRNA and protein show a modest decrease in the postischemic phase. This could contribute to the delayed neuronal death typically seen in the hippocampal formation after transient ischemia.

Scopolamine, a muscarinic antagonist, impairs memory performance in both humans and animals. In this study, repeated measurements of regional cerebral blood flow (rCBF) were made in normal volunteers whilst performing auditory verbal memory tasks, before and after the administration of scopolamine (0.4 mg s.c.) or placebo. Compared to placebo, scopolamine increased blood flow in the lateral occipital cortex bilaterally and the left orbitofrontal region. Scopolamine decreased rCBF in the region of the right thalamus, the precuneus and the right and left lateral premotor areas. Scopolamine attenuated memory-task-induced increases of rCBF in the left and right prefrontal cortex and the right anterior cingulate region. These data suggest that acute blockade of cholinergic neurotransmission affects diverse brain areas, including components of the visual and motor systems, and, in addition, modulates memory task activations at distinct points in a distributed network for memory function.

The effects of traumatic brain injury (TBI) on hippocampal long-term potentiation (LTP) and cellular excitability were assessed at postinjury days 2, 7, and 15. TBI was induced using a well-characterized central fluid-percussion model. LTP of the Schaffer collateral/commissural system was assessed in vivo in urethane-anesthetized rats. Significant LTP of the population excitatory postsynaptic potential (EPSP) slope was found only in controls, and no recovery to control levels was observed for any postinjury time point. Four measurement parameters reflecting pyramidal cell discharges (population spike) indicated that TBI significantly increased cellular excitability at postinjury day 2: (1) pretetanus baseline recording showed that TBI reduced population spike threshold and latency; (2) tetanic stimulation (400 Hz) increased population spike amplitudes to a greater degree in injured animals than in control animals; (3) tetanus-induced population spike latency shifts were greater in injured cases; and (4) tetanic stimulation elevated EPSP to spike ratios (E-S potentiation) to a greater degree in injured animals. These parameters returned to control levels, as measured on postinjury days 7 and 15. These results suggest that TBI-induced excitability changes persist at least through 2 days postinjury and involve a differential impairment of mechanisms subserving LTP of synaptic efficacy and mechanisms related to action potential generation.

The majority of previous modelling studies of vergence and the vestibulo-ocular reflex (VOR) have postulated arbitrary structures mainly on the basis of input-output behavioural relationships. Such models were developed following traditional schemes of oculomotor organization, based upon the notion of independence between different oculomotor subsystems. This impedes the simulation of complex binocular interactions and associated central activities. In contrast to preceding studies, the mathematical model for binocular control presented here was developed fully on physiological and anatomical grounds which reflect the organization and functional properties of known vergence and VOR premotor centres. Computer simulations show the model properly simulates the main observed characteristics in the discharge of several premotor and motor nuclei during slow vergence and the VOR in the dark. In particular, the model reproduces the activity profiles of abducens internuclear neurons, secondary vestibular cells, tonic prepositus hypoglossi neurons and ocular motoneurons during vergence and the VOR. It also simulates the activity of mesencephalic neurons whose discharge is modulated by vergence parameters alone. It is shown that given recent neurophysiological and behavioural findings, ocular reflexes cannot be properly modelled as separate independent subsystems whereas a single, unified modelling approach can produce results consistent with observed data. This study also shows how changes in the functional activity of shared pathways in a single two-sided structure produce vergence and conjugate integrators whose function relies on coupled loops across the brainstem: separate, dedicated operators are not necessary to replicate data. This provides evidence that challenges previous studies supporting the existence of separate vergence and conjugate integrators to transform velocity to position signals in the brainstem. A major implication of this study is that it questions the validity of testing conjugate and vergence systems independently, neglecting potential interactions.

The locomotor activity in the marine mollusc Clione limacina has been found to be strongly excited by serotonergic mechanisms. In the present study putative serotonergic cerebropedal neurons were recorded simultaneously with pedal locomotor motoneurons and interneurons. Stimulation of serotonergic neurons produced acceleration of the locomotor rhythm and strengthening of motoneuron discharges. These effects were accompanied by depolarization of motoneurons, while depolarization of the generator interneurons was considerably lower (if it occurred at all). Effects of serotonin application on isolated locomotor and non-locomotor pedal neurons were studied. Serotonin (5 x 10(-7) to 1 x 10(-6) M) affected most pedal neurons. All locomotor neurons were excited by serotonin. This suggests that serotonergic command neurons exert direct influence on locomotor neurons. Effects of serotonin on nonlocomotor neurons were diverse, most neurons being inhibited by serotonin. Some effects of serotonin on locomotor neurons could not be reproduced by neuron depolarization. This suggests that, along with depolarization, serotonin modulates voltage-sensitive membrane properties of the neurons. As a result, serotonin promotes the endogenous rhythmical activity in neurons of the C. limacina locomotor central pattern generator.

The cortical silent period evoked by magnetic transcranial stimulation and the peripheral silent period were studied in healthy subjects after intravenous injection of diazepam, baclofen or thiopental. None of the drugs tested changed the peripheral silent period. But, unexpectedly, diazepam significantly shortened the cortical silent period, the inhibitory effect lasting about 30 min. In experiments using paired transcranial stimuli, the conditioning shock inhibited the test response to a similar extent with and without diazepam. Although baclofen did not change the cortical silent period, it reduced the size of the H reflex in the forearm muscles. Thiopental also left the duration of the cortical silent period unchanged. These findings show that the cortical silent period can be modified pharmacologically. Diazepam possibly shortens the silent period by modulating GABA A receptors at a subcortical site.

Intracellular recording was made in the C3-C4 segments from cell bodies of a previously described system of propriospinal neurones (PNs), which receive convergent monosynaptic excitation from different higher motor centres and mediate disynaptic excitation and inhibition from them to forelimb motoneurones. Inhibitory effects in these PNs have now been investigated with electrical stimulation of higher motor centres and forelimb nerves. Short-latency IPSPs were evoked by volleys in the cortico-, rubro- and tectospinal tracts and from the reticular formation. Latency measurements showed that those IPSPs which required temporal summation were disynaptically mediated. After transection of the corticospinal tract in C2, only small and infrequent disynaptic IPSPs were evoked from the pyramid. It is postulated that disynaptic pyramidal IPSPs only to a small extent are evoked by monosynaptic excitation of reticulospinal inhibitory neurones known to project directly to the PNs, and that they are mainly mediated by inhibitory interneurones in the C3-C4 segments. Tests with spatial facilitation revealed monosynaptic excitatory convergence from tecto-, rubro- and probably also from reticulospinal fibres on inhibitory interneurones monosynaptically excited from corticospinal fibres (interneuronal system I). Disynaptic IPSPs were also evoked in the great majority of the PNs by volleys in forelimb muscle and skin nerves. A short train of volleys was usually required to evoke these IPSPs from group I muscle afferents. In the case of cutaneous nerves and mixed nerves single volleys were often effective, and the lack of temporal facilitation of IPSPs produced by a train of volleys showed strong linkage from these nerves. The results obtained after transection of the dorsal column at different levels show that the relay is almost entirely rostral to the forelimb segments. Test with spatial facilitation revealed that interneurones monosynaptically activated from forelimb afferents receive convergent excitation from corticospinal but not or only weakly so from tecto- or rubrospinal fibres. There was also convergence from group I muscle afferents and low threshold cutaneous afferents on common interneurones. It is postulated that the disynaptic IPSPs from forelimb afferents are mediated by inhibitory interneurones (interneuronal system II) other than those receiving convergent descending excitation. Volleys in corticospinal fibres, in addition to the disynaptic IPSPs, evoke late IPSPs in the PNs. Similar late IPSPs were evoked from the ipsilateral forelimb by stimulation of the FRA.(ABSTRACT TRUNCATED AT 400 WORDS)

This research investigated the development of visuomotor coordination in childhood, more specifically the conversion of visual information into motor sequences. Three groups of children (aged 6, 8 and 11 years) and a group of adults performed pointing movements without direct feedback from their arm displacements. Visual information, provided by a video camera, was disturbed by rotations of 0 degree, 45 degrees, 90 degrees, 135 degrees or 180 degrees. Six-year-old children showed poor accuracy for 180 degrees rotations. These results suggest that the youngest children use unidirectional representations to convert visual information into motor sequences. At 8 years of age, children showed a shift from unidirectional to bidirectional representations, as reflected by reduced errors for 180 degrees rotations. Eleven-year-old children and adults showed the same type of representations, i.e., bidirectional. However, as reflected by their slower movement time and slower modifications in temporal accuracy across trials, the oldest children have not yet reached maturation in their adaptive process when compared to adults.

When reaching for an object, the proximity of the object, its orientation, and shape should all be correctly estimated well before the hand arrives in contact with it. We were interested in the effects of the object's orientation on manual prehension. Subjects were asked to reach for an object at one of several possible orientations. We found that the trajectory of the hand and its rotation and opening were significantly affected by the object's orientation within the first half of the movement. We also detected a slight delay of the wrist relative to the forearm and a small bias of the orientation of the fingers' tips toward the orientation of the table on which the object lay. Finally, the aperture of the hand was proportional to the physical size of the object, which shows that size constancy was achieved from the variation of the object's orientation. Taken together, these results indicate that the three components of the movement - the transport, rotation, and opening of the hand - have access to a common visual representation of the object's orientation.

We investigated the effect of different spatial and temporal parameters on the saccadic reaction times (SRTs) of the antisaccades and on the frequency and the SRTs of erratic prosaccades in five adult human subjects. The subjects were instructed to aim their saccades to the side opposite to where a visual go-stimulus occurred. Parameters under consideration were: the gap duration (between 0 and 600 ms, and an overlap paradigm); the stimulus size (sizes of 0.1 degrees, 0.2 degrees, and 0.4 degrees, using the gap 200-ms paradigm); and the stimulus eccentricity (1 degree, 2 degrees, 4 degrees, 8 degrees, and 12 degrees, with the gap 200-ms paradigm). A decrease in the anti SRTs and an increase in the error rate were observed with medium gap durations (200 ms, 250 ms), while the anti-SRTs were longer and the error rates lower with the shorter values (0 ms, 100 ms, and with the overlap paradigm) and with the long values (600 ms). A slight decrease in the anti-SRTs and an increase in the error frequency occurred with increasing eccentricity; the SRT distributions of the errors resembled closely those of prosaccades in corresponding prosaccade tasks with the same eccentricities. The stimulus size had only modest or no effects at all. Analysis of the distributions of the correction times of the erratic prosaccades showed that the intersaccadic intervals could be very short: in the range of express saccades, with a peak at 100 ms or in some subjects even shorter, with a peak at 40-50 ms. It is concluded that the performance of antisaccades is influenced by parameters that interact with the fixation and/or attention system of oculomotor control. Parameters supporting a disengagement of fixation at the time of stimulus onset provoke a reduction of the saccadic reaction times not only of prosaccades but also of antisaccades. Moreover, a certain state of disengagement seems to facilitate the occurrence of reflex-like errors.

This study examined the configuration of the vertebral column of the cat during independent stance and in various flexed positions. The range of motion in the sagittal plane is similar across most thoracic and lumbar joints, with the exception of a lesser range at the transition region from thoracic-type to lumbar-type vertebrae. The upper thoracic column exhibits most of its range in dorsiflexion and the lower thoracic and lumbar in ventroflexion. Lateral flexion is limited to less than 5 degrees at all segments. The range in torsion is almost 180 degrees and occurs primarily in the midthoracic region, T4-T11. Contrary to the depiction in most atlases, the standing cat exhibits several curvatures, including a mild dorsiflexion in the lower lumbar segments, a marked ventroflexion in the lower thoracic and upper lumbar segments, and a profound dorsiflexion in the upper thoracic (above T9) and cervical segments. The curvatures are not significantly changed by altering stance distance but are affected by head posture. During stance, the top of the scapula lies well above the spines of the thoracic vertebrae, and the glenohumeral joint is just below the bodies of vertebrae T3-T5. Using a simple static model of the vertebral column in the sagittal plane, it was estimated that the bending moment due to gravity is bimodal with a dorsiflexion moment in the lower thoracic and lumbar region and a ventroflexion moment in the upper thoracic and cervical region. Given the bending moments and the position of the scapula during stance, it is proposed that two groups of scapular muscles provide the major antigravity support for the head and anterior trunk. Levator scapulae and serratus ventralis form the lateral group, inserting on the lateral processes of cervical vertebrae and on the ribs. The major and minor rhomboids form the medial group, inserting on the spinous tips of vertebrae from C4 to T4. It is also proposed that the hypaxial muscles, psoas major, minor, and quadratus lumborum could support the lumbar trunk during stance.

Primary sensory and motor areas of the cerebral cortex contain organised maps of the body. These maps appear to reorganise after damage to the peripheral parts of the sensory or motor systems, so that the cortical representation of undamaged structures expands at the expense of the damaged parts. Several studies in animals have suggested that decreased activity of the inhibitory GABAergic neurones is responsible for driving these changes. However, whether similar mechanisms sustain the effects in the longer term in humans is unknown. The present study addressed this question by examining reorganisation of sensorimotor areas of cortex in six unilateral upper limb amputees several years after the initial injury. We measured two independent indices of GABAergic function. Volumes of distribution of GABA(A) receptors were determined from 11C-flumazenil binding measured with positron emission tomography (PET). The strength of inhibition in the motor cortex was measured with paired-pulse transcranial magnetic stimulation. In the six amputees taken as a whole and compared with 24 normal subjects, there was a highly significant increase in 11C-flumazenil binding in the upper limb region of primary sensorimotor cortex bilaterally and in medial frontal cortex of the hemisphere contralateral to the amputation. Surprisingly, however, there was no change in the time course or strength of intra-cortical inhibition in the motor cortex of the amputees compared with matched control subjects. The increased 11C-flumazenil binding may reflect up-regulation of GABA(A) receptors to compensate for a decrease in the GABA content or activity of inhibitory neurones. Up-regulation of GABA(A) receptors may also indicate that long-term changes require stabilisation of cortical organisation.

For time intervals in the 150-1500 ms range, the difference-discrimination thresholds are about 5%. The value of this Weber fraction varies somewhat depending whether the stimulus modality is vision, hearing or touch. Thresholds are higher when a time interval signaled in one modality has to be compared with one in another, and also when two different modalities are used to delineate a single time interval, as well as when onset and offset are in the same modality but signaled to opposite cortical hemispheres. There is a prominent practice effect. This effect was used to show that there is complete transfer of training between the two visual hemispheres. These findings imply that the time-discrimination mechanism is not located at an early stage of visual processing. If there is a single central time-discrimination apparatus, the observed intermodal differences must relate to the relative ease of access to it via different modalities. The mechanism involved needs elucidating. Counting of spikes or internal time modules would seem to be too simplistic a concept; there is still a need for a process in which the duration of a just concluded presentation and an internally stored interval duration can be compared.

The activity of each of 99 intraparietal neurons was studied in three awake-behaving rhesus monkeys (Macaca mulatta) while subjects performed 100-900 delayed saccade trials. On each trial, a saccadic target was presented at one location selected randomly from a grid of 441 locations spanning 40 degrees of horizontal and vertical visual space. Individual neurons in our population were sensitive to both the direction and amplitude of saccades. Response fields, which plotted firing rate as a function of the horizontal and vertical amplitude of movements for each neuron, were characterized by a Cartesian two-dimensional gaussian model. The goodness-of-fit of these gaussian models was tested by: (1) comparing observed responses with predicted responses for each movement; and (2) by computing the percentage of variance explained by each model. Cartesian Gaussian models provided a good fit to the response fields of most neurons. Across our population, the Gaussian fit to the response field of each neuron accounted for more of the variance in neuronal activity when the data were plotted with regard to the horizontal and vertical amplitude of the saccade than when the same data were plotted with regard to the position of the saccadic target. The Gaussian functions were used to estimate the eccentricity and spatial tuning breadth of each neuronal response field. Modal response field radius was less than 5 degrees, whereas mean response field radius was about 10 degrees. Linear regression analysis demonstrated that response field eccentricity accounted for less than 30% of the variance in response field radius. Analysis of the horizontal distribution of response field centers showed an approximately normal distribution around central fixation. Most histologically recovered neurons were located on the lateral bank of the intraparietal sulcus, although a small number of saccade-related neurons were recorded from Brodmann's area 5 on the medial bank of the intraparietal sulcus.

Delayed neuronal death was produced in the CA1 area of the hippocampus following 5 min of forebrain ischemia in adult gerbils. Immunohistochemistry and Western blotting to Bcl-2, Bax, and Bcl-x was examined in control (age-matched, non-operated and sham-operated) and ischemic gerbils. Bcl-2 immunoreactivity was low in CA1 neurons, but Bax was highly expressed in CA1 neurons of control gerbils. Moderate Bcl-x immunoreactivity was observed in control CA1 neurons. Strong Bcl-2 and Bcl-x immunoreactivity was found in CA1 neurons following ischemia. Bcl-2, Bax, and Bcl-x were localized in dying cells, thus suggesting that expression of Bcl-2 was not sufficient to prevent nerve cells from dying. Although the Bcl-x antibody does not discriminate between Bcl-xL and Bcl-xS content in tissue sections, Western blots disclosed a marked increase in the intensity of the band corresponding to Bcl-xS, but not of the band corresponding to Bcl-xL in ischemic hippocampi, thus indicating that the increase in Bcl-xS is associated with delayed cell death following transient forebrain ischemia in the adult gerbil.

The actions of bath applied histamine on CA1 pyramidal cells were investigated in hippocampal slices of the rat. Histamine caused a) a slight depolarization but no significant change in resting membrane conductance; b) an abbreviation of long afterhyperpolarizations after single action potentials, bursts of action potentials or TTX resistant spikes; c) a loss of accommodation of firing. In the presence of TEA or barium, histamine prolonged and increased the size and number of the slow TTX resistant spikes. A depolarizing plateau which follows such spikes was also increased by histamine, but the population spike was increased. The frequency of spontaneous chloride dependent potentials, which reflect interneurone firing, was also increased. These effects considerably outlasted histamine application and were mimicked by the H2-agonist impromidine but not the H1-agonist thiazolethylamine, and blocked by the H2-antagonists cimetidine and metiamide but not the H1-antagonists mepyramine or the beta-antagonist propranolol. It is concluded that histamine, by activating H2-receptors, antagonizes a calcium mediated potassium conductance in hippocampal pyramidal cells without affecting calcium current. By this mechanism histaminergic afferent fibres could effectively regulate cortical responsiveness by selectively potentiating large excitatory inputs of target neurones.

The human anterior commissure is believed, by extrapolation from data obtained in macaque monkeys, to convey axons from the temporal and orbitofrontal cortex. Reports of interhemispheric transfer and sexual dimorphism related to the anterior commissure, however, make more precise data on the human anterior commissure desirable. We investigated the connectivity of the human anterior commissure in six adults (male and female) that had circumscribed hemispheric lesions in temporal, frontal, parietal or occipital cortices or in infrapallidal white matter using the Nauta for anterogradely degenerating axons. Axons originating in the inferior part of temporal or occipital lobes, occipital convexity and possibly central fissure and prefrontal convexity were found to cross the midsagittal plane in the anterior commissure. The largest contingent of commissural axons originated in the inferior part of the temporal lobe; it displayed a roughly topographic organization, preferentially running through the inferior part of the commissure. The inferior temporal contingent seemed to reach homotopic and heterotopic targets in the opposite hemisphere. Among the latter were the amygdala and possibly the orbitofrontal cortex. The present data suggest that the human anterior commissure conveys axons from much larger territories than expected from work on non-human primates. Similarly to the human and non-human primate corpus callosum, the anterior commissure is roughly topographically organized and participates in heterotopic connectivity.

The binding characteristics of human growth hormone were exploited to identify radioautographically lactogen binding sites in the rat median eminence. Following systemic injection 125I-human growth hormone bound preferentially to the lateral palisade zone, a region of median eminence rich in dopamine and LHRH. Coinjection of 125I-human growth hormone with an excess of unlabeled human growth hormone or ovine prolactin, but not bovine grown hormone, competitively blocked 125I-human growth hormone binding to the external median eminence. These observation provide direct evidence of recognition sites for lactogenic hormones in a discrete region of the median eminence associated with hypothalamic regulation of hypophyseal prolactin and luteinizing hormone secretion. Median eminence lactogen binding sites may mediate presumed direct effect of lactogenic hormones on the reproductive functions of the hypophysiotropic hypothalamus.

The effect of auditory cues at different levels of visual processing was examined by using a visual "conjunction of features" discrimination task (experiment 1) and a "feature" discrimination task (experiment 2). In both experiments the visual target, appearing either on the left or the right of Ss' midline, was preceded by a brief tone either spatially proximal or distal to the target. In the "conjunction" task, subjects had to discriminate the orientation of a T flanked with T distractors of different orientations. In this task, assumed to require focused attention, discrimination accuracy was increased when the sound cue occurred at the subsequent visual target location and was decreased when it occurred at its alternative location. In the "feature" experiment, subjects had to discriminate the orientation of a line segment (+/-45 degrees) presented among line segment distractors. Accuracy was not affected, either when the sound was proximal or when it was distal to the location of the visual target. Results suggest that the early processing of sensory information is modality specific and that interference of auditory stimulation with visual stimuli is more pronounced as the processing of visual stimuli requires focused attention.

Previously, we had described a technique for investigating probable GABAergic cortical inhibitory circuits in conscious man using transcranial magnetic stimulation. This type of inhibition has been termed intracortical inhibition. During voluntary contraction, activity in the circuits responsible for this inhibition is reduced. The mechanism by which this reduction in activity is brought about is unknown. However, evidence exists to suggest that afferent input may be, at least in part, responsible for the reduction in inhibition. The experiments described here were designed to investigate this possibility further. The results of these experiments showed that afferent input, produced by electrical peripheral-nerve stimulation, reduced the level of intracortical inhibition. Also, motor imagery, which activates similar brain regions as overt movement, but does not result in afferent input, failed to produce significant changes in intracortical inhibition. We conclude from these results that afferent input is capable of altering activity in cortical inhibitory circuits. The relevance of these findings to the mechanisms involved in cortical reorganisation is discussed.

The degrees of freedom problem is often posed by asking which of the many possible degrees of freedom does the nervous system control? By implication, other degrees of freedom are not controlled. We give an operational meaning to "controlled" and "uncontrolled" and describe a method of analysis through which hypotheses about controlled and uncontrolled degrees of freedom can be tested. In this conception, control refers to stabilization, so that lack of control implies reduced stability. The method was used to analyze an experiment on the sit-to-stand transition. By testing different hypotheses about the controlled variables, we systematically approximated the structure of control in joint space. We found that, for the task of sit-to-stand, the position of the center of mass in the sagittal plane was controlled. The horizontal head position and the position of the hand were controlled less stably, while vertical head position appears to be no more controlled than joint motions.

Visual information is mapped with respect to the retina within the early stages of the visual cortex. On the other hand, the brain has to achieve a representation of object location in a coordinate system that matches the reference frame used by the motor cortex to code reaching movement in space. The mechanism of the necessary coordinate transformation between the different frames of reference from the visual to the motor system as well as its localization within the cerebral cortex is still unclear. Coordinate transformation is traditionally described as a series of elementary computations along the visuomotor cortical pathways, and the motor system is thought to receive target information in a body-centered reference frame. However, neurons along these pathways have a number of similar properties and receive common input signals, suggesting that a non-retinocentric representation of object location in space might be available for sensory and motor purposes throughout the visuomotor pathway. This paper reviews recent findings showing that elementary input signals, such as retinal and eye position signals, reach the dorsal premotor cortex. We will also compare eye position effects in the premotor cortex with those described in the posterior parietal cortex. Our main thesis is that appropriate sensory input signals are distributed across the visuomotor continuum, and could potentially allow, in parallel, the emergence of multiple and task-dependent reference frames.

Rats were trained on an operant task and then received striatal lesions and grafts. Grafts were derived either from whole-ganglionic eminences or restricted to the lateral eminence. When retested 4 months later; graft-associated behavioural recovery was only apparent with extensive retesting. There was no difference in performance between rats that received whole-dissection or lateral-dissection grafts, and no correlation between performance and the amount of striatal-like (P-zone) tissue within the graft. It is suggested that P-zone reconstruction may be necessary, but not sufficient for behavioural recovery, which may additionally depend upon rehabilitative training.

Impulses in single tactile units innervating the human glabrous skin were recorded percutaneously from the median nerve using tungsten electrodes. The units were classified as belonging to one of the four categories: fast adapting with small receptive fields (FA I), fast adapting with large receptive fields (FA II), slowly adapting with small fields (SA I), and slowly adapting with large fields (SA II). A small test object was lifted, positioned in space and replaced using the precision grip between fingers and thumb. The grip force, the load force (vertical lifting force), the vertical movements of the object and vibrations (accelerations) in the object were recorded. After being virtually silent between lifts, the FA I units whose fields contacted the object became highly active during the initial period of grip force increase (initial response). This was also true for most SA I units. Accordingly, most of the skin deformation changes took place at low grip forces (below ca. 1 N). Later, while the load and grip forces increased in parallel during isometric conditions, the FA I and SA I units continued firing but generally at declining impulse rates. As long as the object was held in the air, the SA I units generally maintained firing with a tendency to adaptation. A minority of the FA I unit also discharged, especially during periods of pronounced physiological muscle tremor. The SA I units usually became silent when the grip and load forces in parallel declined to zero during isometric conditions after the object had contacted the table. However, during the very release of the grip the FA I units and some SA I units showed brief burst discharges (release response). The FA II units responded distinctly to the mechanical transients associated with the start of the vertical movement and especially with the sudden cessation of movement at the terminal table contact. FA II units whose end organs were remotely located in relation to the skin areas in contact with the object also responded. Most FA II units also discharged at the initial touch and at the release of the object, albeit less reliably than the type I units. In addition to weak dynamic responses during the phase of isometric force increase, the SA II units showed comparatively strong tonic responses while the object was held during static conditions. High firing rates also were maintained during long-lasting lifts. Moreover, it was established that the signals in SA II afferents were related to the three dimensional force profile in the grip.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of corticospinal volleys evoked by stimulation of the contralateral pyramid was investigated using intracellular recordings from alpha-motoneurones to forelimb muscles. Confirming and extending previous observations (Illert et al. 1977, Illert and Wiedemann 1984), short latency EPSPs within a disynaptic range were evoked by a train of pyramidal volleys in all varieties of shoulder, elbow, wrist and digit motoneurones. The amplitude of pyramidal EPSPs was sensitive to the stimulus repetition rate. Maximal amplitudes were observed around 2-4 Hz, while at 10 Hz the early EPSP was markedly reduced and the long latency EPSP abolished. The persistence of disynaptic EPSPs after a corticospinal transection in C5/C6 suggested that, for all types of forelimb motor nuclei, disynaptic EPSPs are relayed by C3-C4 propiospinal neurones (PNs) (c.f. Illert et al. 1977). The transection, however, caused a clear reduction in the EPSP of all motoneurone types. After a ventral lesion of the lateral funicle in C5/C6 interrupting the axons of the C3-C4 PNs, disynaptic (and possibly trisynaptic) EPSPs were evoked by a short train of pyramidal volleys. It is postulated that intercalated neurones in a disynaptic cortico-motoneuronal pathway also exist in the forelimb segments. Disynaptic pyramidal IPSPs were observed in most types of forelimb motor nuclei both before and after a corticospinal transection in C5/C6. At all joints, pyramidal excitation dominated in motoneurones to physiological flexors, while in extensor motoneurones mixed excitation and inhibition or dominant inhibition was common. Comparison of pyramidal effects in slow motoneurones (classified according to the after-hyperpolarization duration) to the long head of the triceps and anconeus revealed dominant excitation in the former and inhibition in the latter. It is suggested that the slow motor units in these muscles differ in their function although both muscles are elbow extensors.

We examined single-unit activity in the dorsal premotor cortex for evidence of fast neuronal oscillations. Four rhesus monkeys performed a task in which visuospatial instruction stimuli indicated the direction of forelimb movement to be executed on each trial. After an instructed delay period of 1.5-3 s, movements to either the right or left of a central origin were triggered by a second visuospatial stimulus. From a database of 579 single units, 78 units (13%) contained periodic peaks in their autocorrelation histograms (ACHs), with oscillation frequencies typically 20-30 Hz (mean 27 Hz). An additional 26 units (5%) had oscillatory features that were identified in joint interspike-interval (ISI) plots. Three observations, taken together, suggest entrainment by rhythmic drive extrinsic to these neurons: shuffling ISIs attenuated ACH peaks, indicating a dependency on serial-order effects; oscillation frequency did not change during either increases or decreases in firing rate; and joint ISI plots contained features consistent with a rhythmicity interrupted by intervening discharges. In some cells, oscillations occurred for only one of the two directions of movement. During the delay period, such directional selectivity was observed in 37 units (60% of delay-period oscillators). For at least 17 of these units, we could exclude the possibility that oscillatory directional selectivity resulted from the difficulty in detecting oscillations due to low discharge rates (for one of the two movement directions). Directional selectivity in fast oscillations shows that they can reflect specific aspects of an intended action.

Postischemic spontaneous hyperthermia as a complication of occlusion of the middle cerebral artery with an intraluminal filament has been observed by some authors, but many other reports do not discuss this factor. The possible reasons why some of the authors have not seen severe hyperthermia in their experiments include differences in surgical technique, the strain of animals, the type of the anesthesia, and the occluder filament. The aim of this study was to examine the changes in the core temperature of rats using different types of filaments. The middle cerebral artery was occluded for 2 h with three different types of filaments. The changes in the temperature were continuously monitored during occlusion and for the next 4 h. Groups with uncontrolled hyperthermia and with controlled normal core temperature were used. In addition, the necrotic and penumbral areas were measured 4 and 48 h after the ischemia in both groups. Spontaneous postischemic hyperthermia was detected using all types of filaments. A close correlation was found between the size of the occluder filament and the time-course and degree of hyperthermia. Moreover, the size of the filament correlated well with the size of the infarct at both 4 and 48 h after the occlusion. We suggest that filament size is a major contributor to the degree of hyperthermia and the development of brain damage in the middle cerebral artery occlusion model. Our results call attention to the need to standardize the methods used to screen for therapeutic agents for stroke.

A significant problem in motor control is how information about movement error is used to modify control signals to achieve desired performance. A potential source of movement error and one that is readily controllable experimentally relates to limb dynamics and associated movement-dependent loads. In this paper, we have used a position control model to examine changes to control signals for arm movements in the context of movement-dependent loads. In the model, based on the equilibrium-point hypothesis, equilibrium shifts are adjusted directly in proportion to the positional error between desired and actual movements. The model is used to simulate multi-joint movements in the presence of both "internal" loads due to joint interaction torques, and externally applied loads resulting from velocity-dependent force fields. In both cases it is shown that the model can achieve close correspondence to empirical data using a simple linear adaptation procedure. An important feature of the model is that it achieves compensation for loads during movement without the need for either coordinate transformations between positional error and associated corrective forces, or inverse dynamics calculations.

Experimental neurogenic tumors were induced transplacentally in rats by single injections of ethylnitrosourea (ENU). The resulting primary tumors as well as isogenic transplantation tumor lines and clonal cell lines derived therefrom were examined for their content of the brain specific protein 14-3-2 by a quantitative microcomplement fixation assay. The content of S-100 protein in the samples studied is given as well. Some of the tumors of glial or Schwann cell origin did contain 14-3-2 protein ranging from 0.6 to 1.5 μg 14-3-2 per mg total soluble protein. Our experiments also showed that the ability of a tumor to produce this specific protein is transplantable over a series of subcutaneous isogenic transplantations while in the transplantation tumors the content of this protein seemed to be reduced. We were not able so far to find a correlation between the morphology of a tumor and its capability to produce a specific protein. The clonal cell line RN2 of Schwann cell origin which has been previously described in detail contained both the brain specific proteins 14-3-2 and S-100 in comparable amounts ranging from 0.3 to 0.6 and from 0.4 to 1.0 μg specific protein per total soluble protein respectively.

The projection of C3-C4 propriospinal neurones (PNs) to alpha-motoneurones of forelimb muscles has been analysed with the aid of antidromic stimulation of the ascending branch of the PNs to the lateral reticular nucleus (LRN). A single stimulus of 500 microA applied in the caudo-dorsal part of the LRN evoked a maximal or greater than 90% maximal monosynaptic EPSP in the motoneurones. Systematic mapping of EPSPs evoked by stimulation of 500 microA in and around the LRN revealed that at this strength there was hardly any co-activation of a medial system (Peterson et al. 1979) which evoked small monosynaptic EPSPs with shorter latency and faster time course. The LRN EPSP amplitude was positively correlated with the homonymous group Ia EPSP amplitude, the input resistance and the afterhyperpolarization (AHP) duration. It is therefore postulated that the LRN EPSP amplitude is correlated with motor unit type (Burke 1967, 1968; Burke et al. 1973) with the largest EPSPs in slow (S), the smallest in fast, fatiguable (FF) and possibly intermediate sized in fast, fatigue resistant (FR) units. There was only a small difference in latency of the LRN EPSP in fast and slow motoneurones, while the time course was considerably slower in the latter. It is suggested that slow motoneurones receive projection both from fast and slowly conducting PNs but fast motoneurones mainly from fast PNs. Comparison of the disynaptic pyramidal EPSPs and the LRN EPSPs revealed a positive correlation, but the amplitude ratio pyramidal EPSP: LRN EPSP was smaller in slow than in fast motoneurones. A negative correlation was found between this amplitude ratio and the latency of the disynaptic pyramidal EPSP. It is suggested that this correlation reflects the excitability level in the PNs and that low excitability is due to inhibition of the PNs.

The goal of the present study was to examine the effects of chronic hindlimb unloading on fictive motor patterns which can be developed in hindlimb nerves of adult rats. The animals were divided into two groups. The first group was submitted to hindlimb unloading for 2 weeks by tail suspension. The second group served as controls. After this initial phase, the animals of both groups were acutely decorticated, paralysed and electroneurographic efferent activity was recorded from hindlimb muscle nerves under conditions of "fictive locomotion" in order to evaluate variations in central locomotor command. Fictive rhythmic motor episodes were either spontaneous or evoked by electrical stimulation of the mesencephalic locomotor region. Only the second ones were recognised as locomotor-like activities. The motor pattern was not fundamentally affected by unloading except that, after the unloading period, extensor muscle nerves were significantly more frequently activated and their burst durations were increased compared to activity in control animals, despite the fact that the phasic sensory afferent inputs were suppressed. This suggests that unloading induces plastic modifications of the central networks of neurons implicated in the locomotor command. The origin of this extensor hyperactivity is discussed. It is proposed that it could be the consequence of either changes in motoneuronal properties or of an increase in afferent input to motoneurones.

A voluntary motor act, executed in response to a stimulus, requires both spatial and temporal computation. Even though electrophysiological and positron emission tomography (PET) investigations on humans suggest that SMA, medial prefrontal cortex and primary motor cortex play a role in temporal mechanisms, we have few data about neuronal time computation in the premotor cortex. The involvement of monkey premotor area (PM) in motor learning and cognitive processes, and the presence of buildup neurons, whose activity is closely related to the motor action, prompted us to investigate the involvement of these set-related neurons in the time domain. To this end we manipulated the duration of a pre-cue in a visuomotor task while recording unit activity. We found that, when the duration of the pre-cue was predictable and long (5 s), delay of the onset of cell activity in consecutive trials gradually increased. On the other hand, when the duration was unpredictable or predictable and short (1 s), this phenomenon could not be detected. The inconsistent discharge correlations with expected reward and attentional processes, and the specific discharge relationship to the time instruction, suggest that these buildup neurons reflect a learning process in the time domain.

Handedness is a prominent behavioral phenomenon that emerges from asymmetrical neural organization of human motor systems. However, the aspects of motor performance that correspond to handedness remain largely undetermined. A recent study examining interlimb differences in coordination of reaching demonstrated dominant arm advantages in controlling limb segment inertial dynamics (Sainburg and Kalakanis 2000). Based on these findings, I now propose the dynamic-dominance hypothesis, which states that the essential factor that distinguishes dominant from nondominant arm performance is the facility governing the control of limb dynamics. The purpose of this study is to test two predictions of this hypothesis: 1) adaptation to novel intersegmental dynamics, requiring the development of new dynamic transforms, should be more effective for the dominant arm; 2) there should be no difference in adapting to visuomotor rotations performed with the dominant as compared with the nondominant arm. The latter prediction is based on the idea that visual information about target position is translated into an internal reference frame prior to transformation of the movement plan into dynamic properties, which reflect the forces required to produce movement. To test these predictions, dominant arm adaptation is compared to nondominant arm adaptation during exposure to novel inertial loads and to novel visuomotor rotations. The results indicate substantial interlimb differences in adaptation to novel inertial dynamics, but equivalent adaptation to novel visuomotor rotations. Inverse dynamic analysis revealed better coordination of dominant arm muscle torques across both shoulder and elbow joints, as compared with nondominant arm muscle torques. As a result, dominant arm movements were produced with a fraction of the mean squared muscle torque computed for nondominant arm movements made at similar speeds. These results support the dynamic-dominance hypothesis, indicating that interlimb asymmetries in control arise downstream to visuomotor transformations, when dynamic variables that correspond to the forces required for motion are specified.

In the present study, we investigated the possible mechanisms of cellular injury induced by zinc in rat primary astrocytes and C6 glioma cells. Reactive oxygen species (ROS) production, cellular glutathione (GSH) level and mitochondrial transmembrane potential were examined. Exposure to 200-300 microM Zn2+ for 24 h resulted in significant lactate dehydrogenase (LDH) release in rat primary astrocytes and C6 glioma cells. An exposure of 200 microM Zn2+ resulted in profound morphological changes, for example, shrunken and fragmented nuclei. Pretreatment of a protein synthesis inhibitor, cycloheximide, did not attenuate cellular toxicity induced by Zn2+. Zn2+ exposure increased intracellular ROS levels by about 250%, and depleted cellular GSH within 2 h, which preceded observable LDH release from the cell. Addition of GSH, N-acetylcysteine (NAC) and ascorbic acid substantially attenuated cellular death induced by Zn+ in a concentration dependent manner. ROS production and morphological changes induced by zinc were also inhibited by co-treatment of GSH or NAC with Zn2+. Zn2+ significantly depolarized mitochondrial transmembrane potential, which was reversed by co-treatment of GSH or NAC with zinc. In summary, ROS generation, GSH depletion and mitochondrial dysfunction may be key factors in Zn2+-induced glial toxicity.

Motor learning must involve changes in the organisation of the brain, and it seems axiomatic that afferent signals generated during repeated motor practice contribute to this. In this study, motor-point stimulation of the first dorsal interosseous (FDI) muscle was paired with transcranial magnetic stimulation of the human motor cortex on three successive days to determine whether repeated stimulation sessions result in enduring reorganisation of the motor cortex. This repeated "dual" stimulation induced significant changes in the excitability of the motor cortex together with expansion of the area of scalp from which these responses were elicited. The expansion in muscle representation was accompanied by large movements in the centre of gravity (CoG), suggesting a true reorganisation of the underlying cortical representational zone. The changes persisted for at least 2 days following the last stimulation session. It is concluded that repeated dual stimulation is capable of inducing long-lasting reorganisation within the motor cortex. These changes may be similar in nature to those seen in the motor cortex during motor learning. Moreover, these observations suggest that it may be possible to induce the motor cortex of patients who have suffered strokes to reorganise in a way that improves the voluntary control of the weakened muscles.